Sunday, September 03, 2006

The ‘sour-less’ mouse that solved a tasty mystery.



Our brain constructs a perception of taste from the food we eat. Foods that taste similarly also have some chemical commonality. Actually they taste similar because they have a common chemical group. For example sugars have a glucose moiety, which will be sensed by specialized cells in the tongue, which fire electrical impulses to the brain, which in turn constructs a percept of ‘sweetness’. We perceive many different tastes of which the main basic types are sweet, bitter, sour, salty and umami (taste of monosodium glutamate).

We are able to digest far more chemical groups than the number of tastes we perceive. Why evolution gave us only these five basic tastes is debatable. (I would have liked finer taste discrimination for humans, sometimes Old Monk and Old Cask tastes similar, although I know in my heart of hearts I know they are not). Actually biochemists get into a philosophical argument with psychologists about taste classification, the latter don’t believe in such a classification casting doubts on the physiological basis of such a classification.

The five main basic tastes are thought to signals important information about the food we ingest. Sweet taste is an indicator of how ripe a fruit, which contains more nutrients that raw fruits. Bitter is a good indicator of whether a fruit or plant is poisonous. It makes good sense to evolve a mechanism to know ripe fruits from raw ones and poisonous from non-poisonous. Salty taste evolved probably as an indicator of salt intake since animals have to maintain salts levels to maintain homeostasis and sour taste is elicited by acidic pH, which is abundant in rotten and unripe fruits, which has to be avoided by animals.

Most of the tastes have been well studied in terms of the cell types that sense the molecules and the mechanism that senses these chemicals and makes the cells fire electrical impulses. But the mechanism behind the sour taste was speculative till last week. Some believed that sour and salty taste shared a common mechanism of detection. Many hypotheses were put forward, but there was no proof for anything.

With the Human Genome Project available to fish for genes that could have specific properties, a group at UCSD did just that, fishing out an ion-channel gene that would sense pH (and hence acidity). They found one a gene called PKD2L1. They found that this gene was present in subset of cells in the tongue, which were not sweet, salt or bitter sensors, making it a prime candidate for acid sensing in the tongue.

Now that the cells are found in the tongue, the next question is, what do these cells do? (They could be cells that produce bad language for all we know). So these scientists selectively killed the cells that expressed this gene in mice and tested these animals for their ability to taste. These animals were unable to taste sour taste, although their capacity to detect other tastes was intact, including salty taste. This showed that these cell types were exclusively responsible to the detecting sour taste only. (Wow so neat.)

Adding further feathers to their hats, the group found that these ion-channel genes were also expressed in the central canal of the spinal cord (the small hole that runs through the middle of the spinal cord, where the cerebrospinal fluid runs through). This fits into an even older story. The acid sensing mechanism is important in many ways to an organism, to maintain the functional state of body fluids. For example pH is the way to detect the carbon-di-oxide levels in blood and CSF. The cellular basis of pH sensing mechanism is not known in the CSF. This ion-channel PKD2L1 could be the mechanism that senses pH in CSF being expressed in the edge of the central canal and also firing action potentials for minor changes in pH.

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